Zhao Tong, Qi Jianni, Liu Tiantian, Wu Hao, Zhu Qiang
Department of Gastroenterology, Shandong Provincial Hospital, Cheeloo College of Medicine, Shandong University, Jinan, China.
Central Laboratory, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, China.
Front Med (Lausanne). 2022 Mar 2;9:821710. doi: 10.3389/fmed.2022.821710. eCollection 2022.
N6-methyladenosine (m6A) modification has been demonstrated to play an important part in hepatitis B virus (HBV) infection and immune response. This study aims to further investigate whether m6A modification plays an important role in the progression of HBV-related liver fibrosis through the regulation of immune cell infiltration.
In this study, 124 chronically HBV infected cases were obtained from the Gene Expression Omnibus database. In total, 489 m6A-and-stage related genes were selected to be associated with the m6A modification and the stage of liver fibrosis. Based on these genes, we identified two distinct gene clusters, gene clusterA and gene clusterB. The immune characteristics of the two clusters were comprehensively compared. The m6A-S score was constructed as quantification of individual m6A status. The correlations between m6A regulators and infiltrating immune cells were examined and compared in different pairs of groups with various m6A traits.
Biological functions, immune cell infiltration, and cytokines expression were compared between the two gene clusters proving that the gene clusterB was more immune active and had a more advanced liver fibrosis stage. The m6A-S score was associated with immune infiltration and the progression of liver fibrosis. Five different grouping conditions with different m6A traits were set up. According to the intersection of significant genes and cells, interacting with macrophage and interacting with nature killer T cells may be key points in the progress of liver fibrosis.
N6-methyladenosine modification is closely related to the immune cell infiltration and the fibrosis stage of chronic HBV-infected liver tissue. It provides us a better understanding of the progression of liver cirrhosis evaluating the m6A modification pattern and immune infiltration characteristics.
N6-甲基腺苷（m6A）修饰已被证明在乙型肝炎病毒（HBV）感染和免疫反应中起重要作用。本研究旨在进一步探讨m6A修饰是否通过调节免疫细胞浸润在HBV相关肝纤维化进展中发挥重要作用。
本研究从基因表达综合数据库中获取了124例慢性HBV感染病例。总共选择了489个与m6A和阶段相关的基因，这些基因与m6A修饰和肝纤维化阶段相关。基于这些基因，我们鉴定出两个不同的基因簇，基因簇A和基因簇B。全面比较了这两个簇的免疫特征。构建m6A-S评分作为个体m6A状态的量化指标。在具有不同m6A特征的不同组对中检查并比较了m6A调节因子与浸润免疫细胞之间的相关性。
比较了两个基因簇之间的生物学功能、免疫细胞浸润和细胞因子表达，证明基因簇B具有更强的免疫活性且肝纤维化阶段更 advanced。m6A-S评分与免疫浸润和肝纤维化进展相关。设置了五种具有不同m6A特征的分组条件。根据显著基因与细胞的交集，与巨噬细胞相互作用和与自然杀伤T细胞相互作用可能是肝纤维化进展的关键点。
N6-甲基腺苷修饰与慢性HBV感染肝组织的免疫细胞浸润和纤维化阶段密切相关。它为我们更好地理解肝硬化的进展提供了帮助，可通过评估m6A修饰模式和免疫浸润特征来实现。
